Antigen-presenting cells (APCs) participate in the initiation of the inflammatory process in various immune-mediated dermatoses through the activation of antigen-specific T lymphocytes. The skin contains several different subsets of APCs. To investigate the role of these APCs in T-cell immune-mediated inflammation, we examined the distribution and numbers of epidermal and dermal CD1a⁺ dendritic cells (DCs), factor XIIIa⁺ dermal DCs, and CD68⁺ macrophages in five T-cell-mediated inflammatory skin diseases. Immunohistochemistry of CD1a, factor XIIIa, and CD68 was performed using paraffin-embedded tissue obtained from a total of 51 patients with eczematous dermatitis (histologically spongiotic dermatitis), psoriasis, lichen planus, acute graft-versus-host disease (GVHD), and chronic GVHD. The numbers of positive cells for each staining were compared with those in site-matched normal skin control specimens from aged-matched subjects. In spongiotic dermatitis and lichen planus, the numbers of epidermal and dermal CD1a⁺ cells and factor XIIIa⁺ cells were significantly greater than in normal control skin, while in psoriasis only factor XIIIa⁺ cells were significantly increased in number. Acute and chronic GVHD showed a reduced number of dermal CD1a⁺ cells. Interestingly, factor XIIIa⁺ cells were decreased in acute GVHD while they were increased in chronic GVHD. There was a significant reduction in epidermal CD1a⁺ cells in acute GVHD, but not in chronic GVHD. The differences in the numbers of APCs in lesional skin appeared to reflect differences in the pathophysiology of these inflammatory skin diseases.